Asymmetric ruthenium complexes, rhodium complexes and iridium complexes, which take sulfonyl diamine as a ligand, are useful asymmetric reducing catalysts. These are employed for the asymmetric reduction of a ketone substrate for an efficient production of an optically active alcohol (Patent Literatures 1 and 2).
In Non-patent Literature 1,2-propanol is used as a hydrogen source. This reaction is a reversible equilibrium reaction that gives an optically active alcohol and acetone from ketone substrate and 2-propanol. Therefore, an (S,S) catalyst, for example, reduces acetophenone to give (S)-phenylethanol in a ratio of 99:1 ((S):(R)). However, this reaction preferentially dehydrogenates (S)-phenylethanol in a ratio of 99:1 to give acetophenone, compared to (R)-phenylethanol. Therefore, at initial phase of the reaction, when the concentration of the hydrogen source 2-propanol is high, (S)-phenylethanol and (R)-phenylethanol are produced in the reaction system in a ratio of 99:1. However, when the reaction proceeds and the concentration of (S)-phenylethanol is increased, the reverse reaction will reduce the composition ratio (optical purity) of (S)- and (R)-phenylethanols in the reaction system; their ratio will be reduced to 97:3 at 75% conversion. As being such an equilibrium reaction, in a reaction system where 2-propanol is employed as hydrogen source, in order to obtain an optically active alcohol in high optical purity, there have been problems that there must be a large excessive amount of the hydrogen source 2-propanol than the product optically active alcohol; and that the reaction must be carried out under the condition where the concentration of the ketone substrate is as low as approximately 0.1M.
In order to solve these problems, in Non-patent Literature 2, formic acid is used as the hydrogen source. In this method, formic acid is eliminated from the system as carbon dioxide after providing hydrogen, rendering the reaction irreversible and increasing the optical purity of the produced optically active alcohol. Although using this method, the optical purity and the S/C ratio (substrate/catalyst molar ratio) of the optically active alcohol were improved compared to the reaction using 2-propanol as the hydrogen source, there still is a necessity of improvement, such as in the S/C ratio (substrate/catalyst molar ratio).
Then Non-patent Literature 3 suggested a method to use sodium formate as the hydrogen source under a condition of a two-phase reaction system where water is employed as the solvent. In this method, although there is a large increase in the reaction rate and an improvement in the S/C ratio (substrate/catalyst molar ratio) compared to the reaction using formic acid, the optical purity of the alcohol is decreased. For example, a reaction of an acetophenone gives phenylethanol at 97% ee using formic acid, whereas a two-phase reaction system gives phenylethanol at 95% ee.
Meanwhile, a high catalytic activity of the two-phase reaction system is interpreted to be an effect exhibited by water (Non-patent Literatures 3 and 4), and therefore, in Non-patent Literature 5, many of the approaches for achieving a high optical purity were focused on the structural optimization of the catalyst and the development of an aqueous catalyst, while leaving the condition unchanged that water is present. On the other hand, Non-patent Literature 6 reported as an approach to improve the reacting conditions, a homogenous reaction system in which potassium formate in polyethyleneglycol is used as a hydrogen source. This approach, however, is focused on the recycle of catalyst by retaining the catalyst in polyethyleneglycol phase, and there is no mentioning about any suppressive effect on the racemization of the produced alcohol by the homogenous reaction.